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10.2215/CJN.03270314

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suck abstract from ncbi


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pmid25873267
      Clin+J+Am+Soc+Nephrol 2015 ; 10 (6 ): 1021-30
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  • Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism #MMPMID25873267
  • Sprague SM ; Wetmore JB ; Gurevich K ; Da Roza G ; Buerkert J ; Reiner M ; Goodman W ; Cooper K
  • Clin J Am Soc Nephrol 2015[Jun]; 10 (6 ): 1021-30 PMID25873267 show ga
  • BACKGROUND AND OBJECTIVES: Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm. RESULTS: Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent of treatment arm, participants with reductions in P or Ca×P were significantly more likely to show reductions in FGF-23. CONCLUSIONS: During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism.
  • |*Renal Dialysis/adverse effects [MESH]
  • |Aged [MESH]
  • |Australia [MESH]
  • |Biomarkers/blood [MESH]
  • |Calcimimetic Agents/adverse effects/*therapeutic use [MESH]
  • |Calcium/blood [MESH]
  • |Canada [MESH]
  • |Chi-Square Distribution [MESH]
  • |Cinacalcet/adverse effects/*therapeutic use [MESH]
  • |Female [MESH]
  • |Fibroblast Growth Factor-23 [MESH]
  • |Fibroblast Growth Factors/*blood [MESH]
  • |Humans [MESH]
  • |Hyperparathyroidism, Secondary/blood/diagnosis/*drug therapy [MESH]
  • |Kidney Failure, Chronic/blood/complications/diagnosis/*therapy [MESH]
  • |Logistic Models [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Parathyroid Hormone/blood [MESH]
  • |Phosphorus/blood [MESH]
  • |Prospective Studies [MESH]
  • |Risk Factors [MESH]
  • |Russia [MESH]
  • |Time Factors [MESH]
  • |Treatment Outcome [MESH]
  • |United States [MESH]


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